The overall goal of the General Clinical Research Center (GCRC) at Dallas is to provide an optimal setting for clinical investigation which will lead to improved understanding of the disease process, allow better methods of diagnosis and treatment, foster interdisciplinary collaboration, and offer training in clinical investigation. Major activities of the GCRC include: Development of a safe and effective treatment of postmenopausal osteoporosis with intermittent slow-release sodium fluoride, based on a randomized trial, and incorporating a new reflection ultrasound device to assess bone quality; determination of the importance of calcitriol excess or sensitivity in nephrolithiasis due to absorptive hypercalciuria and in idiopathic osteoporosis and evaluation of treatment with a new slow-release neutral potassium phosphate (UroPhos-K); examination of the causes and management of primary hypercholesterolemia (elevated low density lipoproteins) and hypoalphalipoproteinemia (reduced high density lipoproteins); evaluation of erythrocyte galactitol accumulation as a surrogate for the direct measurement of erythrocyte aldose reductase and ascertainment of whether erythrocyte galactitol levels may predict high susceptibility to diabetic complications; determination of the safety and efficacy of anti-ICAM-1 (anti-adhesion molecule antibodies) in the treatment of rheumatoid arthritis; performance of a clinical trial of ursodeoxycholic acid and methotrexate in the treatment of patients with primary biliary cirrhosis; delineation of the regulation of cytolytic lymphocytes, which are involved in pulmonary immune defense and tissue injury, by pulmonary macrophages, and utilization of exercise testing, biochemical measurements and 31-phosphorus magnetic resonance spectroscopy to elucidate and intervene in disorders of muscle energy metabolism.